Personalized and Precision Medicine Journal
Where Innovations Meets Personalized and Precision Medicine

Analysis of EGFR gene mutations in tissue samples of lung cancer tumors

Document Type : Original Article

Authors

Blnd Ibrahim Mohammed 1
Amir Mohammadi 2
Nafise Poorhasan 3

1 Biology Department, College of Science, Salahaddin University-Erbil, Erbil, Iraq

2 Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Mazandaran

3 Personalized Medicine Research Center of AmitisGen, Tehran, Iran

https://doi.org/10.22034/pmj.2020.43451
Abstract
Lung cancer is the leading cause of cancer deaths worldwide. Approximately 25% of nonsmall-cell lung cancers have mutations in the EGFR gene, most of which occur in hotspot regions in exons 18, 19, 20, and 21. In-frame deletions in exon 19 (~50%) and the L858R point mutation in exon 21 (~40%) are associated with a favorable response to EGFR tyrosine kinase inhibitors. In this study, mutations of two exons of 19 and 21 in 50 lung cancer tumor samples were investigated by the sequence method. From 50 lung cancer patients, 8 (16%) patients had an L858R (c.2573T>G) mutation, 6 (12%) patients had deletion type 1a mutation, and one patient had deletion type 1b mutation. Examining the sequence of candidate genes associated with lung cancer can be very important in choosing the right treatment approach.

Keywords

Lung cancer
EGFR gene
sequencing
drug resistance
TKI
  1. Gazdar AF. Activating and resistance mutations of EGFR in non-smallcelllung cancer: role in clinical response to EGFR tyrosine kinase inhibitors.Oncogene 2009;28(Suppl 1):S24–S31.
  2. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermalgrowth factor receptor underlying responsiveness of non-small-celllung cancer to gefitinib. N Engl J Med 2004;350:2129–2139.
  3. Yang CH, Yu CJ, Shih JY, et al. Specific EGFR mutations predict treatmentoutcome of stage IIIB/IV patients with chemotherapy-naïve nonsmall- cell lung cancer receiving first-line gefitinib monotherapy. J ClinOncol 2008;26:2745–2753.
  4. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009;361:947–957.
  5. Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small cell lung cancer with mutated EGFR. N Engl J Med 2010;362:2380–2388.
  6. Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small lung cancer harboring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomized phase 3 trial. Lancet Oncol 2010;11:121–128.
  7. Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-smallcell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol 2011;12:735–742.
  8. Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicenter, open-label, randomized phase 3 trial. Lancet Oncol 2012;13:239–246.
  9. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, firstline study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol 2011;29:2866–2874.
  10. Han JY, Park K, Kim SW, et al. First-SIGNAL: first-line single-agent iressa versus gemcitabine and cisplatin trial in never-smokers with adenocarcinoma of the lung. J Clin Oncol 2012;30:1122–1128.
  11. Chung KP, Wu SG, Wu JY, et al. Clinical outcomes in non-small cell lung cancers harboring different exon 19 deletions in EGFR. Clin Cancer Res 2012;18:3470–3477.
  12. Taron M, Mayo C, de Aguirre I, et al. Outcome to erlotinib in non-small cell lung cancer patients with EGFR in-frame deletions of exon 19 according to the size of the deletion. J Clin Oncol 2010;28:15s(Suppl):Abstr 7549
  13. Cancer Therapy Evaluation Program, Common Terminology Criteria forAdverse Events, Version 3at:http://ctep.cancer.gov/protocolDevelopment/ electronic_applications/docs/ctcaev3.pdf. Accessed Jan11, 2011.
  14. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92:205–216.
  15. Tam IY, Chung LP, Suen WS, et al. Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features. Clin Cancer Res 2006;12:1647–1653.
  16. Su KY, Chen HY, Li KC, et al. Pretreatment epidermal growth factor receptor (EGFR) T790M mutation predicts shorter EGFR tyrosine kinase inhibitor response duration in patients with non-small-cell lung cancer. J Clin Oncol 2012;30:433–440.
  17. Maheswaran S, Sequist LV, Nagrath S, et al. Detection of mutations in EGFR in circulating lung-cancer cells. N Engl J Med 2008;359:366–377.
  18. Regales L, Balak MN, Gong Y, et al. Development of new mouse lung tumor models expressing EGFR T790M mutants associated with clinical resistance to kinase inhibitors. PLoS One 2007;2:e810.
  19. Wu JY, Yu CJ, Chang YC, Yang CH, Shih JY, Yang PC. Effectiveness of tyrosine kinase inhibitors on “uncommon” epidermal growth factor receptor mutations of unknown clinical significance in non-small cell lung cancer. Clin Cancer Res 2011;17:3812–3821.
  20. Schiller JH, Harrington D, Belani CP, et al; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced nonsmall- cell lung cancer. N Engl J Med 2002;346:92–98.
  21. Catalogue of Somatic Mutations in Cancer. Available at: http://www. sanger.ac.uk/genetics/CGP/cosmic/. Accessed August 1, 2012.
  22. Douillard JY, Shepherd FA, Hirsh V, et al. Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial. J Clin Oncol 2010;28:744–752.
Personalized and Precision Medicine Journal
Volume 5, Issue 17
Original article
Spring 2020
Pages 1-4

  • Receive Date 26 July 2020

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